Air conditioners are designed to cool down a certain space, which is why they must be sized to your home space and your ductwork. You can certainly reduce ductwork size in a remodeling project, but keep in mind that ducts are a certain size for a reason. Using smaller ducts means that air will not be able to circulate as quickly.
In other circumstances, you may be well justified in reducing the size of your ductwork upstairs. This is especially true if you have an older house with larger ducts and are switching to a newer air conditioner, or if you are trying to improve flow. Modern air conditioners are made for small duct sizes, so reducing the size of old ducts can help you save money while using your system correctly.
Airflow and air friction are the primary concerns when changing air-duct size. If you change air ducts and make them too small, then the air will not be able to flow quickly enough to cool rooms as it should and your energy costs will rise. Air friction refers to the twists and turns the air must make before leaving the vents. Add too many, and the air will not be able to circulate properly.
If you want to change your second story ductwork but are having second thoughts about reducing the duct size, look into a ductless AC remodel, which bypasses ducts completely and provides the second story with its own evaporator. You can also run an outside air line up from your original evaporator and vent in through the wall to skip the ductwork. Compare prices on the different projects to see which would work best for you.